The objective of the project is to investigate the role of growth and differentiation factors in bone and cartilage. Special emphasis is placed on initiation factors in bone development. osteogenin is a prototypic example of a bone development initiation factor. The projects currently under investigation with the salient findings are: 1) Cloning and expression of osteogenin genes; 2) Production and characterization of antibodies to synthetic peptides to "active sites" in osteogenin; 3) Interaction of osteogenin with various extracellular matrix macromoles. Osteogenin binds with high affinity to type IV collagen. This finding has important developmental implications; 4) Expression of tissue specific genes in response to osteogenin; 5) Autoradiographic localization of binding sites to osteogenin in developing embryos; 6) The differentiation of osteoblastic cell processes on type IV collagen and other substrata, and 7) Application of osteogenin in craniofacial defects in primates. Recent work has demonstrated the utility of osteogenin in correction of massive craniofacial defects.